1. Field of the Invention
The present invention relates to novel, readily water-soluble bis[N-{3,5-bis-(hydroxyalkylaminocarbonyl)-2,4,6-triiodo-phenyl}-N-(.alpha .-hydroxyacyl)-amino]-alkanes for use as X-ray contrasting agents.
2. Description of the Prior Art
5-Acylamino-2,4,6-triiodo-isophthalic acid diamides and their use in X-ray contrasting materials is disclosed in Swiss Pat. No. 544,551. The compounds contain only simple, unsubstituted aliphatic acyl groups, generally acetyl groups. Certain members of this class of compounds which contain carbohydrate residues possess sufficient water-solubility, for example, 3-acetylamino-N-methyl-acetylamino-2,4,6-triiodo-benzoyl-glucosamine which has become known under the international non-proprietary name of METRIZAMIDE. In this connection, see also compound No. 11 of U.S. Pat. No. 3,701,771, British Pat. No. 1,321,591, Swiss Pat. No. 544,551, Austrian Pat. No. 318,134 and German Offenlegungsschrift No. 2,031,724, as well as publications of T. Almen, S. Salvesen, K. Golman: Acta Radiologia Suppl. 335 (1973), pages 1-13, 233-75, and 312-38. A disadvantage of this compound is that it is difficult to synthesize and particularly, that it is relatively unstable. This limits significantly its usability and makes the handling of the material difficult.
1-5-.alpha.-hydroxypropionylamino-2,4,6-triiodo-isophthalic-acid-bis-(1,3-d ihydroxyisopropylamide), known under the international non-proprietary name of IOPAMIDOL, represents an advance over this art. In this connection, see also German Pat. No. 2,547,789, British Pat. No. 1,472,050, U.S. Pat. No. 4,001,323 and the article by Felder et al., IL FARMACO, Ed. Sc. 32, 835-844 (1977). This compound is distinguished by an essentially simpler structure, by higher stability, by being easier to isolate and by a relatively lower viscosity of its concentrated aqueous solutions. The toxicity of this compound is very low.
Developments in recent years have shown clearly that it is extremely difficult and only infrequently possible to find non-ionic compounds which have the specific properties required for the individual techniques of X-ray contrast investigations. These required properties are a true water-solubility, sufficient for producing stable, that is, not supersaturated, concentrated solutions, maximum general and neurotropic tolerance, minimum osmolality, a relatively high viscosity which can be matched for the specific end use, a maximum stability towards hydrolytic effects, and a structure which is sufficiently simple to make its synthesis economically feasible as well as to simplify its isolation and purification.